1. FIELD OF THE INVENTION
This invention relates to a therapeutic composition and to methods of preparing compositions containing the sedative hypnotic drug methaqualone or the like compounds and their acid addition salts as well as to a method for the manufacture of methaqualone or the like compounds in solid dosage preparations to enhance the rate of solution and absorption of methaqualone or the like compounds, thereby producing a more rapid and/or greater degree of sedation or hypnosis for a given weight of said sedative agents.
2. DESCRIPTION OF THE PRIOR ART
Methaqualone, i.e., 2-methyl-3-(o-tolyl)-4(3H)-quinazolinone is a known, orally effective compound with valuable hypnotic, anticonvulsant, and sedative properties which is used in therapy as central nervous system calmative agent and central muscle relaxant. Boissier et al. describe in "Therapie" vol. 22, pp. 129-135 (1967) a number of 2-methyl-3-phenyl-4(3H)-quinazolinone compounds which are substituted in the phenyl ring by other substituents than methyl and which also possess hypnotic, anticonvulsant and sedative properties. Especially valuable compounds of this group are 2-methyl-3-(2-chloro phenyl)-4(3H)-quinazolinone known as mecloqualone, 2-methyl-3-(2,4-dichlorophenyl)-4(3H)-quinazolinone, 2-methyl-(2-chloro-4-methylphenyl)-4(3H)-quinazolinone, 2-methyl-3-(4-chlorophenyl)-4(3H)-quinazolinone, and other compounds of the formula ##STR1## wherein R.sub.1 is chloro or lower alkyl such as methyl or ethyl, and
R.sub.2 is hydrogen, chloro, or methyl. PA1 a. a surfactant (0.5% to 300%, by weight), and/or PA1 b. an acidifier (10% to 1000%, by weight), and/or PA1 c. an aggregation preventing carrier, i.e. a carrier providing a large surface of methaqualone or the like compounds (100% to 2000%, by weight), and/or PA1 d. a dispersant (0.5% to 50%, by weight), PA1 a. Deposition of the particles of the drug from their solution on the solubilizing adjuncts, preferably on the carrier. PA1 b. Micronizing of the drug or its salts without aggregation together with the adjuncts and especially with the carrier and/or the dispersant. PA1 c. Spray drying of solutions or suspensions of the drug or its salts together with one or more of the adjuncts, PA1 d. Dissolving of the drug or its salts in the molten adjuncts such as a meltable surfactant, and causing solidification of the molten mixture under conditions whereby the drug will crystallize in a fine state of subdivision.
To be effective after oral administration, a sedative or hypnotic agent such as methaqualone or the like compounds in a solid dosage form such as a tablet or capsule must be available for absorption from the gastrointestinal tract. For a sedative or hypnotic agent to act promptly, such absorption should occur very soon after ingestion of the drug. The first step in absorption is the dissolution of the active components in the gastric juice. Furthermore, rapid dissolution of the active compound would result not only in a more rapid absorption and pharmacologic response, but also in more complete absorption of the drug from the gastrointestinal tract, i.e., a high percentage of the drug will be absorbed and will exert its intended action if it dissolves rapidly and completely.
The heretofore available solid dosage forms of methaqualone and the like compounds, however, have the disadvantage that their rate of dissolution and absorption from the gastro-intestinal tract is rather low and that, therefore, less satisfactory sedative or hypnotic effects are achieved.